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HIV InfectionsPhase 3NCT03164564

Evaluating the Safety and Efficacy of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women

A Phase 3 study testing Oral CAB, Oral TDF/FTC and CAB LA in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 20 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This study will evaluate the safety and efficacy of the long-acting injectable agent cabotegravir (CAB LA) compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) in HIV-uninfected women. Read more about this study

Who is it for?
Ages 18 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for
HIV Infections
What is being tested?
Oral CAB, Oral TDF/FTC and CAB LA
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
3,224 participants
Where
20 sitesin 7 countries
Study dates
7 Nov 2017to 17 Oct 2026
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Born female
  • 18-45 years at the time of screening
  • Willing and able to provide informed consent
  • Willing and able to undergo all required study procedures
  • Non-reactive HIV test results at Screening and Enrollment. Note: HIV-uninfected, based on HIV test results obtained at Screening and just prior to randomization at the Enrollment visit. All HIV test results from the Screening visit must be obtained and must all be negative/non-reactive. This includes testing for acute HIV infection, which must be performed within 14 days of Enrollment. In addition, at least one HIV test result using blood drawn at the Enrollment visit must be obtained prior to randomization into the study and must be negative/non-reactive. Individuals who have one or more reactive or positive HIV test result(s) will not be enrolled, even if subsequent confirmatory testing indicates that they are not HIV-infected (see SSP Manual). Those with any enrollment HIV test result positive will proceed through the HIV algorithm per the SSP but will not be able to receive study product regardless of subsequent test results.
  • Sexually active (i.e., vaginal intercourse on a minimum of two separate days in the 30 days prior to Screening)
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  • Score of greater than or equal to 5 using a modified VOICE risk score
  • No plans to re-locate or travel away from the site for greater than or equal to 8 consecutive weeks during study participation
  • Creatinine clearance of greater than or equal to 60 mL/min (using Cockcroft-Gault equation) (use sex at birth for calculation)
  • Although not protocol exclusionary, sites should carefully consider the advisability of enrolling participants with calculated creatinine clearance between 60-70 mL/min, as limited changes in creatinine clearance during study conduct will lead to protocol-mandated product holds and may alter the risk-benefit considerations of study participation
  • Hepatitis B virus (HBV) surface antigen (HBsAg) negative and accepts vaccination
  • Alanine aminotransferase (ALT) less than 2 x upper limit of normal (ULN) and total bilirubin (Tbili) less than or equal to 2.5 x ULN
  • HCV antibody negative
  • If of reproductive potential (defined as pre-menopausal women who have not had a sterilization procedure per self-report, such as hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy), must have a negative beta human chorionic gonadotropin (βHCG) pregnancy test (sensitivity of less than or equal to 25 mIU/mL) performed (and results known) on the same day as and before initiating the protocol-specified study product(s) at Enrollment.
  • Have documented evidence of surgical sterilization, OR documented evidence of no uterus (e.g., hysterectomy), OR must agree to use a reliable form of long acting contraception, during the trial and for 52 weeks after stopping the long acting injectable, or 30 days after stopping oral study product, from the list below:
  • Intrauterine device (IUD) or intrauterine system (IUS) that meets less than 1% failure rate as stated in the product label
  • Hormone-based contraceptive that meets less than 1% failure rate when used consistently and correctly as stated in the product label (implants or injectables only; this excludes combined oral contraception)
  • No medical condition that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical history and examination or in available medical records)
  • No alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical history and examination or in available medical records)

Who cannot join

  • One or more reactive HIV test results at Screening or Enrollment, even if HIV infection is not confirmed
  • Pregnant or currently breastfeeding, or intends to become pregnant and/or breastfeed during the study
  • Co-enrollment in any other HIV interventional research study (provided by self-report or other available documentation), with one exception: IMPAACT 2026 (co-enrollment in IMPAACT 2026 is permitted for participants who become pregnant)
  • Current or past enrollment in an HIV vaccine or broadly neutralizing antibody trial
  • Current or chronic history of liver disease (e.g., non-alcoholic or alcoholic steatohepatitis) or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones, or cholecystectomy)
  • History of seizure disorder, per self-report
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  • Clinically significant cardiovascular disease, as defined by history/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease
  • Inflammatory skin conditions that compromise the safety of IM injections, per the discretion of the Investigator of Record (IoR). Mild skin conditions may not be exclusionary at the discretion of the IoR or designee
  • Has a tattoo or other dermatological condition overlying the buttock region which in the opinion of the IoR or designee may interfere with interpretation of injection site reactions (ISRs)
  • Coagulopathy (primary or iatrogenic) which would contraindicate IM injection
  • Active or planned use of prohibited medications as described in the Investigator Brochure (IB) or listed in the Study Specific Procedures Manual (SSP) (provided by self-report, or obtained from medical history or medical records)
  • Known or suspected allergy to study product components (active or placebo), including egg or soy products (egg and soy products are contained in Intralipid)
  • If potentially able to conceive, unwilling to adhere to long acting contraception (IUD/IUS, injection, or implant) with a less than 1% failure rate when used consistently and correctly as stated in the product package insert/ manufacturer's guidelines

Trial locations and contacts

20 sites in 7 countries.

20 sites in 7 countries

South Africa7 sites

  • Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS

    Cape Town, Western Cape, 7505

  • Emavundleni CRS

    Cape Town, Western Cape, 7750

  • Botha's Hill CRS

    Durban, KwaZulu-Natal, 3660

  • Isipingo CRS

    Isipingo, KwaZulu-Natal, 4110

  • Soweto HPTN CRS

    Johannesburg, Gauteng, 1862

  • Ward 21 CRS

    Johannesburg, Gauteng, 2001

  • Verulam CRS

    Verulam, KwaZulu-Natal, 4340

Other trials in South Africa

Zimbabwe5 sites

  • Zengeza CRS

    Chitungwiza, Mashonaland East Province

  • Seke South CRS

    Chitungwiza

  • St Mary's CRS

    Chitungwiza

  • Milton Park CRS

    Harare

  • Spilhaus CRS

    Harare

Other trials in Zimbabwe

Uganda3 sites

  • UVRI-IAVI HIV Vaccine Program LTD. CRS

    Entebbe

  • Baylor-Uganda CRS

    Kampala

  • MU-JHU Research Collaboration (MUJHU CARE LTD) CRS

    Kampala

Other trials in Uganda

Malawi2 sites

  • Blantyre CRS

    Blantyre

  • Malawi CRS

    Lilongwe, Central Region

Other trials in Malawi

Botswana1 site

  • Gaborone CRS

    Gaborone, South-East District

Other trials in Botswana

Eswatini1 site

  • Eswatini Prevention Center CRS

    Mbabane

Other trials in Eswatini

Kenya1 site

  • Kisumu Crs

    Kisumu, Nyanza, 40100

Other trials in Kenya

About this study

Official title: A Phase 3 Double Blind Safety and Efficacy Study of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women

This study will evaluate the safety and efficacy of the long-acting injectable agent cabotegravir (CAB LA) compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) in HIV-uninfected women.

Read the detailed description

The purpose of this study is to evaluate the safety and efficacy of the long-acting injectable integrase inhibitor cabotegravir (CAB LA) compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) in a population of sexually active HIV-uninfected women at risk for HIV.

This study will take place in three steps. Participants will be randomly assigned to one of two arms:

Arm A:

Step 1: Participants will receive daily oral CAB and TDF/FTC placebo for 5 weeks.

Step 2: Participants will receive injections of CAB LA at two time points 4 weeks apart and every 8 weeks thereafter and daily TDF/FTC placebo beginning at Week 5.

Arm B:

Step 1: Participants will receive daily TDF/FTC and oral CAB placebo for 5 weeks.

Step 2: Participants will receive daily TDF/FTC and intramuscular (IM) placebo injections at two time points 4 weeks apart and every 8 weeks thereafter beginning at Week 5.

Step 2 will continue until the last enrolled participant reaches approximately 76 weeks on Step 2 (Week 81 for the last enrolled participant).

In Step 3, all participants (Arms A and B) will receive daily TDF/FTC for up to 48 weeks, starting no later than 8 weeks after the last injection.

At the end of Step 3, all participants will then transition to locally available HIV prevention services, including services for PrEP, if available.

Study visits will occur at Day 0 and at Weeks 2 and 4 during Step 1. During Step 2, participants will attend up to 24 visits, depending on when they enroll in the study. Study visits will occur every 12 weeks during Step 3. Study visits may include physical examinations; blood, urine, and vaginal swab collection; risk reduction, adherence counseling, and contraception counseling.

HPTN 084-01 is a sub-study of HPTN 084. The purpose of this study is to examine the safety, tolerability, and acceptability of CAB LA for the prevention of HIV among adolescent females. Participants will receive oral CAB for 5 weeks, followed by 34 weeks on CAB LA, then quarterly visits for 48 weeks after final injection. All participants who have received at least one injection will be followed for 48 weeks after their last injection. Total study duration per participant will be approximately 21 months.

Conditions
HIV Infections
Being tested
Oral CAB, Oral TDF/FTC, Placebo for oral CAB, Placebo for oral TDF/FTC, CAB LA
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral CABDrug

    Also called Cabotegravir

    CAB 30 mg tablet

  • Oral TDF/FTCDrug

    Also called Tenofovir disoproxil fumarate/emtricitabine, Truvada

    TDF/FTC 300 mg/200 mg fixed dose combination tablet

  • Placebo for oral CABDrug

    Placebo tablets

  • Placebo for oral TDF/FTCDrug

    Placebo tablets

  • CAB LADrug

    Also called Cabotegravir long-acting injectable

    600 mg administered as one 3 mL (600 mg) intramuscular injection in the gluteal muscle

  • Placebo for CAB LADrug

    Administered as one 3 mL intramuscular injection in the gluteal muscle

Study groups in NCT03164564
Study groupRoleWhat they receive
Arm A: CAB + Placebo TDF/FTC + CAB LAExperimentalDuring Step 1, participants will receive daily oral CAB and oral TDF/FTC placebo for 5 weeks. In Step 2, participants will receive injections of CAB LA at two time points 4 weeks apart and every 8 weeks thereafter and daily oral TDF/FTC placebo beginning at Week 5. In Step 3, participants will receive daily TDF/FTC for up to 48 weeks, starting no later than 8 weeks after the last injection.
Receives: Drug: Oral CAB; Drug: Oral TDF/FTC; Drug: Placebo for oral TDF/FTC; Drug: CAB LA
Arm B: TDF/FTC + Placebo CAB + Placebo CAB LAActive comparatorDuring Step 1, participants will receive daily TDF/FTC and oral CAB placebo for 5 weeks. In Step 2, participants will receive daily TDF/FTC and placebo for CAB LA injections at two times points 4 weeks apart and every 8 weeks thereafter beginning at Week 5. In Step 3, participants will receive daily TDF/FTC for up to 48 weeks, starting no later than 8 weeks after the last injection.
Receives: Drug: Oral TDF/FTC; Drug: Placebo for oral CAB; Drug: Placebo for CAB LA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Pariicipants With Documented Incident HIV Infections

    The number of participants with an incident HIV infection that is confirmed by the HPTN Laboratory Center and Endpoint Adjudication Committee.

    Measured: HIV tests at enrollment, weeks 2, 4, and 5, then every 4 weeks through week 25, then every 8 weeks. Analyzed through week 185 or the date of DSMB decision to unblind all participants, whichever is earliest.

  2. Number of Participants Who Experienced Grade 2 or Higher Clinical and Laboratory Adverse Events (AEs) in Steps 1 and 2

    AEs will be summarized using MedDRA System Organ Class and preferred terms.

    Measured: Treatment emergent AE measured with onset date through participant's last study visit, or the date of DSMB decision to unblind all participants, whichever is earliest. Assessed at each visit (injections visits q 8 weeks and safety visits q 8 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2017
  2. Study start7 Nov 2017
  3. Primary completion5 Nov 2020
  4. Study completion17 Oct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
3,224 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03164564
Sponsor's protocol ID
HPTN 084
Other IDs
38070
Status last verified
Sep 2025
First submitted
22 May 2017
Last updated
9 Oct 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Marzinke MA, Han K, Hanscom B, Guo X, Piwowar-Manning E, Hendrix CW, Rose S, Spooner E, Mathew C, Innes S, Sekabira R, Mutambanengwe M, Rooney JF, Rinehart AR, Adeyeye A, Cohen MS, Hosseinipour M, Ford SL, Delany-Moretlwe S. Pharmacologic evaluation of delayed long-acting cabotegravir administration among cisgender women in HPTN 084. Antimicrob Agents Chemother. 2024 Nov 6;68(11):e0099424. doi: 10.1128/aac.00994-24. Epub 2024 Sep 23.

    PubMed 39311597

  • Delany-Moretlwe S, Hughes JP, Bock P, Ouma SG, Hunidzarira P, Kalonji D, Kayange N, Makhema J, Mandima P, Mathew C, Spooner E, Mpendo J, Mukwekwerere P, Mgodi N, Ntege PN, Nair G, Nakabiito C, Nuwagaba-Biribonwoha H, Panchia R, Singh N, Siziba B, Farrior J, Rose S, Anderson PL, Eshleman SH, Marzinke MA, Hendrix CW, Beigel-Orme S, Hosek S, Tolley E, Sista N, Adeyeye A, Rooney JF, Rinehart A, Spreen WR, Smith K, Hanscom B, Cohen MS, Hosseinipour MC; HPTN 084 study group. Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial. Lancet. 2022 May 7;399(10337):1779-1789. doi: 10.1016/S0140-6736(22)00538-4. Epub 2022 Apr 1.

    PubMed 35378077

  • Scarsi KK. Chasing the cabotegravir tail: implications for prevention. Lancet HIV. 2020 Jul;7(7):e451-e453. doi: 10.1016/S2352-3018(20)30165-X. Epub 2020 Jun 1. No abstract available.

    PubMed 32497490

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Oral CAB, Oral TDF/FTC and CAB LA in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 20 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in South Africa, Zimbabwe, Uganda, Malawi, Botswana and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Pariicipants With Documented Incident HIV Infections (time frame: HIV tests at enrollment, weeks 2, 4, and 5, then every 4 weeks through week 25, then every 8 weeks. Analyzed through week 185 or the date of DSMB decision to unblind all participants, whichever is earliest.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03164564, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2025.

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